Sandbox 44

=Trypsin=

PDB code: 1QLQ Molecular Weight: 6481.5

Trypsin is a serine protease that is produced in the pancreas. Broken down, a serine protease is an enzyme that cleaves amino acid sequences and contains a serine amino acid residue in the active site of the enzyme. In order to prevent it from breaking down the proteins of the organism that produces it, it is first produced as the inactive zymogen, proenzyme trypsinogen.

Structural Aspects


Trypsin is an enzyme that is composed of one, sequence unique, chain consisting of 58 amino acid residues. Observing the Rainbow Coloration of trypsin one can easily follow the primary sequence of the amino acids as it begins at the amide or N-terminal end(dark blue), and progresses to the carboxyl or C-terminal end with the final 58th amino acid residue (red).

After establishing the primary sequence, the secondary structure of a protein in determined by the hydrophobic effect. As hydrophobic molecules seek to be located near the center of the molecule, while hydrophilic regions seek to be located along the exterior, this fear and love of water becomes the greatest determining force in the secondary and tertiary folding of the protein. Looking at the Secondary Structure of trypsin one can see it is composed of two alpha helices(pink) and two beta sheets(yellow).

Holding these secondary structures together is a network of hydrogen bonds that help stabilize these structures. Looking first at the hydrogen bonding in the protein backbone one can begin to see the importance of hydrogen bonds in alpha helices and beta sheets. Looking at the hydrogen bonding in the side chains, one can further see how it serves to stabilize these secondary structures.

Trypsin's tertiary structures is held together by three Disulphide bonds located between the 5 and 55, 14 and 38, and 30 and 51 Cystine residues(yellow). Disulphide's covalent bonds are a major stabilizing force in the tertiary structure of the enzyme. Besides disulphide bonds a salt bridge is also present and holds the N and C terminal ends together, further stabilizing the protein.

To determine the polar and non-polar sections of an enzyme(the forces behind the secondary and tertiary structures), the various R groups coming off of the protein's backbone must be analyzed. Looking at the R groups, the side chains can be classified as either non-polar (hydrophobic) or polar (hydrophilic). Looking first at the ball and stick model you can easily see the classifications of the nonpolar(pink) and polar(yellow) side chains. Looking at this molecule you can see the majority of the yellow strands are found near the exterior of the enzyme where they would act with the polar environment, while many of the nonpolar residues are hidden inside. Looking at the space filling model you can achieve a better grasp on the organization of these nonpolar and polar sections of the enzyme. Polar regions again appear in yellow, nonpolar pink, and some of the waters that would interact with the enzyme appear gray.

Looking at the structure you will notice three SO4 and a single SO2 molecules (sulfur yellow, oxygen red). These play no part in the function or role of the enzyme but were simply used to help stabilize the protein for crystallization so its three dimensional structure could be recorded and analyzed.

Function
In biological applications trypsin is used to cleave and break down proteins. Due to the nature of trypsin's active site it cleaves on the C-terminal(or carboxyl) end of lysine and arginine amino acid residues, except when this C-terminal end is attached to proline (as its rigid structure sterically inhibits the enzyme). The yellow ball and stick residues show the active site, while the green section shows the aspartic acid residue. As aspartic acid is deprotonated at physiological pH, it carries a negative charge, and easily attracts the positively charged lysine and arginine residues to the active site where they can be cleaved by trypsin.

Medical Importance and Other Applications
Cystic Fibrosis is a disease in which the body fails to properly transport trypsin and other enzymes from the pancreas.

Imbalances of trypsin and other related proteins are believed to play a role in disorders like emphysema, asthma, arthritis, skin disorders, and cancerous tumor growth.

Trypsin is used with a combination of bromelain and rutin to relieve pain and improve function joint for individuals suffering from osteoarthritis.

Trypsin is used in wound cleansing and healing as it helps remove dead tissue and improve healing time.

Trypsin is added to baby food to help pre-digest the proteins to help babies digest it.

Trypsin is also used as a digestion aid to help individuals who lack enzymes needed for digestion.